Authors: Cirella A, Berraondo P, Di Trani CA, Melero I Abstract IL-12 is a very potent cancer immunotherapy agent but is difficult to harness safely if given systemically. Local gene-transfer aims to confine the effects of IL-12 to malignant tissues, thus avoiding toxicity. Lipid-nanoparticled messenger RNA achieves IL-12 expression and efficacy in mouse models, opening the way to an ongoing trial. PMID: 33004432 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Authors: PMID: 33004470 [PubMed - in process] (Source: Clinical Cancer Research)
Authors: Marmarelis ME, Bauml JM Abstract The APOLLO investigators showed that NGS of cerebrospinal fluid can reveal molecular alterations - how should this affect our management approach? PMID: 32998958 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: These data show the potential of statins as pharmacologic modulators of endocytic proteins for improved tumors' accumulation of monoclonal antibodies. The translational significance of these findings lies in the potential of statins to temporarily modulate the heterogeneous presence of receptors at the cell membrane, a characteristic often associated with poor response in tumors to therapeutic antibodies. PMID: 32998959 [PubMed - as supplied by publisher] (Source: Clinical Cancer...
CONCLUSIONS: Together, these data suggest that itacitinib has potential as a prophylactic agent for the prevention of CAR T-cell-induced CRS, and a phase II clinical trial of itacitinib for prevention of CRS induced by CAR T-cell therapy has been initiated (NCT04071366). PMID: 32998963 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: There is a subset of tumors, frequently classified as mesenchymal or IGS cluster 23, that may be identified with immunohistochemistry and could well be optimal candidates to immunotherapy. PMID: 32998960 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSION: Triplet therapy with endocrine therapy and mTOR and CDK4/6 inhibition provides clinical benefit and an acceptable safety profile in previously treated postmenopausal women with HR+, HER2- ABC. PMID: 32998962 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: The onvansertib and decitabine combination was well tolerated and had anti-leukemic activity particularly in patients with target engagement and decreased mutant ctDNA following treatment. This combination will be further investigated in the ongoing phase 2 trial. PMID: 32998961 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: Certain survivors are more susceptible to cisplatin-induced neurotoxicity, markedly increasing likelihood of developing numerous neuro-otological symptoms that affect quality of life. Genome-wide analysis identified genetic variation in FAM20C as a potentially important risk factor. PMID: 32998964 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: Alvocidib can be safely administered prior to 7+3 induction with encouraging clinical activity. These findings warrant further investigation of alvocidib combinations in newly diagnosed AML. This study was registered at clinicaltrials.gov identifier NCT03298984. PMID: 32998965 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: The RP2D of Debio 1143 is 200 mg/day for 14 days, q3w when combined with concomitant high-dose cisplatin chemoradiotherapy in LA-SCCHN. Debio 1143 addition to chemoradiotherapy was safe and manageable. Preliminary efficacy is encouraging and supports further development. PMID: 32994295 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: Our study highlights importance of defects of DNA repair machinery in NPC pathogenesis and their prognostic values for clinical implications. These signatures will be useful for patient stratification to evaluate conventional and new treatment for precision medicine in NPC. PMID: 32988965 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: Enzalutamide with exemestane was well tolerated. While PFS was not improved by the addition of enzalutamide to exemestane in an unselected population, ET-native patients with high AR mRNA, particularly in combination with low ESR1 mRNA levels, may benefit from enzalutamide with exemestane. PMID: 32988969 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Authors: Ishak CA, De Carvalho DD Abstract Genome-wide DNA methylation profiles of serous tubal intraepithelial lesions (STICs) resemble methylation profiles of HGSOCs more closely than normal fallopian tube epithelium. While STICs and HGSOCs share subsets of common hypermethylated regions, DNA methylation can distinguish STICs from HGSOCs to provide proof-of-principle that DNA methylation can identify HGSOC initiation. PMID: 32988966 [PubMed - as supplied by publisher] (Source: Clinical...
CONCLUSIONS: Combined tumor volume measurement and estimation of tumor regression and growth rate has potential to enhance assessment of treatment effects in clinical studies of colorectal cancer that would not be achieved with conventional, RECIST-based unidimensional measurements. PMID: 32988968 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: AZD4320 is a potent molecule with manageable thrombocytopenia risk to explore the utility of a dual Bcl-2/Bcl-xL inhibitor across a broad range of tumor types with dysregulation of Bcl-2 pro-survival proteins. PMID: 32988967 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSION: outcome after post-transplant relapse among younger patients has improved significantly in recent years, likely reflecting, among other factors, the efficacy of post-transplant salvage including second allo-HCT. PMID: 32988970 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: CDK12-altered mCRPCs have worse prognosis with these tumors surprisingly being primarily enriched for CD4+FOXP3- cells that seem to associate with worse outcome and may be immunosuppressive. PMID: 32988971 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: These studies provide preclinical rationale to test CDK4/6i + RT in women with locally-advanced ER+ breast cancer at high risk for locoregional recurrence. PMID: 32967938 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Authors: Sengupta R, Honey K PMID: 32967942 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSION: Large pre-treatment contrast-enhancing tumor mass and higher ADC identify patients who may experience a survival benefit from bevacizumab plus radiotherapy. Persistent 18FET-PET signal of no longer contrast-enhancing tumor after concomitant bevacizumab plus radiotherapy suggests pseudoresponse and predicts poor outcome. TRIAL REGISTRATION: NCT01443676. PMID: 32967939 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: We present the first large-scale profiling of autoantibodies in advanced prostate cancer, utilizing a new antibody profiling approach to reveal novel cancer-specific antigens and epitopes. Our study recovers antigens of known importance and identifies novel tumor-specific epitopes of translational interest. PMID: 32967941 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Authors: Marcus L, Donoghue M, Aungst S, Myers CE, Helms WS, Shen G, Zhao H, Stephens O, Keegan P, Pazdur R Abstract The Food and Drug Administration (FDA) approved entrectinib on August 15, 2019, for the treatment of adult and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and...
Authors: Chang E, Weinstock C, Zhang L, Charlab R, Dorff SE, Gong Y, Hsu V, Li F, Ricks TK, Song P, Tang S, Waldron PE, Yu J, Zahalka E, Goldberg KB, Pazdur R, Theoret MR, Ibrahim A, Beaver JA Abstract On December 18, 2019, the Food and Drug Administration (FDA) granted accelerated approval to enfortumab vedotin-ejfv (PADCEV; Astellas and Seattle Genetics) for treatment of patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1 or PD-L1 inhibitor,...
CONCLUSION: PAM50MET is prognostic in HR+/HER2-negative MBC, and further evaluation might help identify candidates for ET only or novel therapies. PMID: 32962980 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: The SADA-BsAb platform safely delivered large doses of radioisotopes to tumors and demonstrated no toxicities to the bone marrow, kidneys or liver. Due to its modularity, SADA-BsAbs can be easily adapted to most tumor antigens, tumor types, or drug delivery approaches to improve TI and maximize the delivered dose. PMID: 32958698 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSION: Lenalidomide is efficacious with manageable toxicities as an early intervention strategy in patients with high-risk CLL, but did not enhance humoral response to PCV13 vaccine. This trial was registered with ClinicalTrials.gov Identifier: NCT01351896. PMID: 32958702 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: This is the first large GWAS ever conducted in mCRC patients treated with first-line standard treatment in a randomized phase III trial. A common SNP in AXIN1 confers worse OS and the effect is replicated in TCGA. Further studies in CRC experimental models are required. PMID: 32958699 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Authors: Nusrat M Abstract Most colorectal cancers are microsatellite stable with no response to anti-PD-1 therapy, necessitating the development of new immunomodulatory treatment strategies. Co-inhibition of anti-PD-1 and STAT3 can elicit an effective anti-tumor response in a small subset of microsatellite stable colorectal cancer patients, and biomarkers predictive of response are under investigation. PMID: 32958701 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: Our comprehensive analysis of sequencing data generated from a large cohort of PDAC patient samples highlights a distinctive pattern of bi-allelic CDKN2A mutation in EOPC tumors. Increased expression of FOXC2 in EOPC, with the correlation between FOXC2 and EMT pathways, represent novel molecular characteristics of EOPC. PMID: 32958704 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Authors: Bhat J, Kabelitz D Abstract The use of checkpoint monotherapy in treating cancer has limited success. Post-translational modifications (PTM) of proteins such as glycosylation might have clinical implications due to distinct modifications found in diseases and its regulatory role in the immunometabolic gene expression. Such novel mechanistic targets hold great promise for combined immunotherapy. PMID: 32958703 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Authors: Sun J, Lu Q, Sanmanmed MF, Wang J Abstract Immunomodulatory agents blocking the PD-1/PD-L1 pathway have shown a new way to treat cancer. The explanation underlying the success of these agents may be the selective expression of PD-L1 with dominant immune-suppressive activities in the tumor microenvironment (TME), supporting a more favorable tumor response-to-toxicity ratio. However, despite the big success of these drugs, most cancer patients show primary or acquired resistance,...
CONCLUSIONS: Pexidartinib in pediatric pts was well tolerated at all DL tested, achieved target inhibition and resulted in a weight based RPD2 dose. PMID: 32943455 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: High AREG mRNA expression is a favorable prognostic biomarker for mCRC which interacted significantly with efficacy of anti-EGFR treatment. PMID: 32943459 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: Concurrent administration of enzalutamide and crizotinib resulted in a clinically significant 74% decrease in systemic crizotinib exposure. Further investigation of this combination in CRPC is not planned. Our results highlight the importance of evaluating pharmacokinetic interactions when evaluating novel combination strategies in CRPC. PMID: 32943461 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: STAT3 ASO treatment reverses a suppressive TME and promotes pro-inflammatory gene expression changes in patients' tumors and mouse models. Preclinical data provide evidence that ASO-mediated inhibition of STAT3 in the immune compartment is sufficient to remodel the TME and enhance the activity of checkpoint blockade without direct STAT3 inhibition in tumor cells. Collectively, these data provide rationale for testing this combination in the clinic. PMID: 32943458 [PubMed - as supplied...
CONCLUSION: Treatment with PPE and erlotinib combination was well tolerated in patients with APLs of the head and neck, and showed a high rate of pathologic response with excellent CFS. This combination deserves further investigation for the chemoprevention and/or prevention of second primary tumors in early stage head and neck cancer. PMID: 32943457 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Authors: Champiat S, Tselikas L, Farhane S, Raoult T, Texier M, Lanoy E, Massard C, Robert C, Ammari S, De Baere T, Marabelle A Abstract Systemic immunotherapies such as immune checkpoint blockade targeted at PD(L)1 and CTLA4 have demonstrated their ability to provide durable tumor responses and long term overall survival benefits for some patients in several solid tumor types. However, a majority of patients remain resistant to these treatments and a significant proportion of them develop...
CONCLUSIONS: ILC metastases harbor genomic alterations that may potentially explain endocrine resistance in a large proportion of patients, and present genomic differences as compared to IDC metastases. PMID: 32943456 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSION: Palbociclib in combination with trastuzumab is safe and exhibits promising survival outcomes in trastuzumab pre-treated ER-positive/HER2-positive advanced breast cancer with a PAM50 luminal A or B subtype. The enrollment was stopped prematurely and a new randomized cohort was opened in this population. PMID: 32938620 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Authors: Tang B, Chi Z, Chen Y, Liu X, Wu D, Chen J, Song X, Wang W, Dong L, Song H, Wu H, Feng H, Yao S, Qin S, Zhang X, Guo J PMID: 32934029 [PubMed - in process] (Source: Clinical Cancer Research)
CONCLUSIONS: Serum IL-6 and YKL-40 are potential new prognostic biomarkers in BTC. IL-6 provides independent prognostic information and may be superior to CA19-9 in certain contexts. Moreover, anti-IL-6R should be considered as a new treatment option to sustain gemcitabine response in BTC patients. PMID: 32933994 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
CONCLUSIONS: This study indicates PPI use is a negative prognostic marker in advanced urothelial carcinoma treated with ICI therapy, but not chemotherapy. Furthermore, the analysis suggests PPIs influence the magnitude of ICI efficacy, and this warrants further investigation. PMID: 32933995 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Authors: Yang H, Mao W, Rodriguez-Aguayo C, Mangala LS, Bartholomeusz G, Iles LR, Jennings NB, Ahmed AA, Sood AK, Lopez-Berestein G, Lu Z, Bast RC PMID: 32934031 [PubMed - in process] (Source: Clinical Cancer Research)
CONCLUSIONS: We anticipate that combined TSPO PET/IGS represents a translational approach for precision pancreatic cancer care through discrimination of high-risk indeterminate lesions and actionable surgery. PMID: 32933996 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Authors: PMID: 32934028 [PubMed - in process] (Source: Clinical Cancer Research)
CONCLUSIONS: These results suggest that YAP, MEK1/2, and lysosome function are necessary and critical targets for the therapy of GNAQ/11-driven melanoma, and identify trametinib plus hydroxychloroquine as a potential treatment strategy for metastatic uveal melanoma. PMID: 32933997 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Authors: Ryu D, Kim SJ, Hong Y, Jo A, Kim N, Kim HJ, Lee HO, Kim K, Park WY PMID: 32934030 [PubMed - in process] (Source: Clinical Cancer Research)
CONCLUSIONS: Collectively, these results demonstrate the all-in-one potential of 64Cu-RaftRGD for imaging-guided radiotherapy of OCPM by targeting both tumoral neovessels and cancerous cells. Based on the ITD finding, we propose that pairing αVβ3- and hypoxia-targeted radiotherapies could improve therapeutic efficacy by overcoming the heterogeneity of ITD encountered with single-agent treatments. PMID: 32933998 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Authors: Wang D, Müller S, Ruhul Amin ARM, Huang D, Su L, Hu Z, Rahman MA, Nannapaneni S, Koenig L, Chen Z, Tighiouart M, Shin DM, Chen ZG PMID: 32934033 [PubMed - in process] (Source: Clinical Cancer Research)
Authors: Chan N, Willis A, Kornhauser N, Ward MM, Lee SB, Nackos E, Seo BR, Chuang E, Cigler T, Moore A, Donovan D, Cobham MV, Fitzpatrick V, Schneider S, Wiener A, Guillaume-Abraham J, Aljom E, Zelkowitz R, Warren JD, Lane ME, Fischbach C, Mittal V, Vahdat L PMID: 32934032 [PubMed - in process] (Source: Clinical Cancer Research)
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου